Short H2A histone variants are expressed in cancer

Short H2A (sH2A) histone variants are primarily expressed in the testes of placental mammals. Their incorporation into chromatin is associated with nucleosome destabilization and modulation of alternate splicing. Here, we show that sH2As innately possess features similar to recurrent oncohistone mut...

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Bibliographic Details
Published in:Nature communications 2021-01, Vol.12 (1), p.490-490, Article 490
Main Authors: Chew, Guo-Liang, Bleakley, Marie, Bradley, Robert K., Malik, Harmit S., Henikoff, Steven, Molaro, Antoine, Sarthy, Jay
Format: Article
Language:English
Subjects:
631/67/68/2486
631/67/69
Alternative Splicing
Animals
Arrays
Cancer
Chromatin
Destabilization
Development Biology
Epigenomics
Female
Gene Expression Regulation, Neoplastic
Genomics
Histones
Histones - genetics
Histones - metabolism
Human health and pathology
Humanities and Social Sciences
Humans
Life Sciences
multidisciplinary
Mutation
Neoplasms - genetics
Neoplasms - metabolism
Nucleosomes
Placenta
Pregnancy
Science
Science (multidisciplinary)
Spermatogenesis
Splicing
Stability analysis
Testes
Up-Regulation
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Summary:Short H2A (sH2A) histone variants are primarily expressed in the testes of placental mammals. Their incorporation into chromatin is associated with nucleosome destabilization and modulation of alternate splicing. Here, we show that sH2As innately possess features similar to recurrent oncohistone mutations associated with nucleosome instability. Through analyses of existing cancer genomics datasets, we find aberrant sH2A upregulation in a broad array of cancers, which manifest splicing patterns consistent with global nucleosome destabilization. We posit that short H2As are a class of “ready-made” oncohistones, whose inappropriate expression contributes to chromatin dysfunction in cancer. Short H2A variants are testis-specific histones that destabilize nucleosomes during spermatogenesis. In this study, the authors show that these variants are expressed in an array of different cancers and identify splicing changes associated with nucleosome instability in these malignancies.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-020-20707-x